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DOI: 10.3748/wjg.v21.i44.12635
Retrospective Study
Management and associated factors of delayed perforation
after gastric endoscopic submucosal dissection
Haruhisa Suzuki, Ichiro Oda, Masau Sekiguchi, Seiichiro Abe, Satoru Nonaka, Shigetaka Yoshinaga,
Takeshi Nakajima, Yutaka Saito
Haruhisa Suzuki, Ichiro Oda, Masau Sekiguchi, Seiichiro
Abe, Satoru Nonaka, Shigetaka Yoshinaga, Takeshi
Nakajima, Yutaka Saito, Endoscopy Division, National Cancer
Center Hospital, Tokyo 104-0045, Japan
Author contributions: Suzuki H and Oda I designed the study,
analyzed and interpreted the data, and wrote the draft; Sekiguchi
M, Abe S, Nonaka S, Yoshinaga S, Nakajima T, and Saito Y
contributed to the critical revisions of the article for important
intellectual content; all authors had final approval of this article.
Informed consent statement: All study participants, or their
legal guardian, provided informed written consent prior to study
enrollment.
Conflict-of-interest statement: No conflict of interest was
declared by the authors.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was
selected by an in-house editor and fully peer-reviewed by external
reviewers. It is distributed in accordance with the Creative
Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this
work non-commercially, and license their derivative works on
different terms, provided the original work is properly cited and
the use is non-commercial. See: http://creativecommons.org/
licenses/by-nc/4.0/
Correspondence to: Haruhisa Suzuki, MD, Endoscopy Division,
National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo
104-0045, Japan. harusuzu@ncc.go.jp
Telephone: +81-3-35422511-7794
Fax: +81-3-35423815
Received: May 25, 2015
Peer-review started: May 27, 2015
First decision: June 19, 2015
Revised: July 15, 2015
Accepted: September 30, 2015
Article in press: September 30, 2015
Published online: November 28, 2015
WJG|www.wjgnet.com
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
© 2015 Baishideng Publishing Group Inc. All rights reserved.
ORIGINAL ARTICLE
Abstract
AIM: To identify the actual clinical management and
associated factors of delayed perforation after gastric
endoscopic submucosal dissection (ESD).
METHODS: A total of 4943 early gastric cancer (EGC)
patients underwent ESD at our hospital between
January 1999 and June 2012. We retrospectively
a s s e s s e d t h e a c t u a l m a n a g e m e n t o f d e l aye d
perforation. In addition, to determine the factors
associated with delayed perforation, after excluding
123 EGC patients with perforations that occurred
during the ESD procedure, we analyzed the following
clinicopathological factors among the remaining 4820
EGC patients by comparing the ESD cases with delayed
perforation and the ESD cases without perforation: age,
sex, chronological periods, clinical indications for ESD,
status of the stomach, location, gastric circumference,
tumor size, invasion depth, presence/absence of
ulceration, histological type, type of resection, and
procedure time.
RESULTS: Delayed perforation occurred in 7 (0.1%)
cases. The median time until the occurrence of delayed
perforation was 11 h (range, 6-172 h). Three (43%)
of the 7 cases required emergency surgery, while
four were conservatively managed without surgical
intervention. Among the 4 cases with conservative
management, 2 were successfully managed endo­
scopically using the endoloop-endoclip technique. The
median hospital stay was 18 d (range, 15-45 d). There
were no delayed perforation-related deaths. Based
on a multivariate analysis, gastric tube cases (OR =
11.0; 95%CI: 1.7-73.3; P = 0.013) were significantly
associated with delayed perforation.
CONCLUSION: Endoscopists must be aware of not
only the identified factors associated with delayed
perforation, but also how to treat this complication
12635 November 28, 2015|Volume 21|Issue 44|
 Suzuki H et al . Delayed perforation from gastric ESD
effectively and promptly.
Key words: Early gastric cancer; Endoscopic submucosal
dissection; Delayed perforation; Emergency surgery;
Conservative management
© The Author(s) 2015. Published by Baishideng Publishing
Group Inc. All rights reserved.
Core tip: In this study, delayed perforation occurred in
0.1% (7 cases) of 4943 early gastric cancer patients
undergoing endoscopic submucosal dissection (ESD);
43% (3 cases) of these cases required emergency
surgery. This study also showed that the gastric tube
was an independent risk factor associated with delayed
perforation. This study is significant because it clarified
both the clinical management and risk factors of
delayed perforation based on data from a large series
of consecutive patients undergoing ESD. Endoscopists
must be aware of not only the identified factors
associated with delayed perforation, but also how to
treat this complication effectively and promptly.
Suzuki H, Oda I, Sekiguchi M, Abe S, Nonaka S, Yoshinaga
S, Nakajima T, Saito Y. Management and associated factors
of delayed perforation after gastric endoscopic submucosal
dissection. World J Gastroenterol 2015; 21(44): 12635-12643
Available from: URL: http://www.wjgnet.com/1007-9327/full/
v21/i44/12635.htm DOI: http://dx.doi.org/10.3748/wjg.v21.
i44.12635
INTRODUCTION
Endoscopic submucosal dissection (ESD) is widely
used in East Asia (e.g., Japan and Korea) as an
initial treatment for early gastric cancer (EGC) with a
negligible risk of lymph node (LN) metastasis, even
for cases that involve large and ulcerative lesions .
[1-4]
The therapeutic outcomes of gastric ESD are excellent;
however, there are still cases of various complications,
[5,6]
such as bleeding and perforation . ESD procedure-
related perforations can be subdivided into perforations
that occur during gastric ESD and delayed perforations
occurring after the completion of gastric ESD. Most
perforations occur during gastric ESD, and the risk
of perforation reportedly ranges from 1.2% to 9.6%
for gastric ESD
[5-12]
. The majority of perforation
cases can be treated conservatively using complete
endoscopic closure with endoclips
[5,6,13]
. In contrast,
delayed perforation is a rare (with an incidence of
0.43% to 0.45%) but serious complication that
[6,14-20]
sometimes requires emergent surgery . Under
these circumstances, the actual clinical management
and the associated factors of delayed perforation
induced by gastric ESD should be clarified to minimize
its incidence and to treat this complication effectively
and promptly. Although several reports have described
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delayed perforation after gastric ESD, no published
report has thoroughly evaluated the various factors
associated with delayed perforation based on data from
a large series of consecutive EGC patients undergoing
ESD
[14-20]
. Therefore, we attempted to identify the
actual clinical management and the associated factors
of delayed perforation induced by ESD for EGC based
on our extensive clinical experience.
MATERIALS AND METHODS
Patients
A total of 4943 EGC patients (male:female ratio,
3.9:1; median age, 69 years; range, 27-96 years)
underwent ESD at our hospital between January
1999 and June 2012. The clinicopathological findings
of these 4943 EGC patients are shown in Table 1. In
our hospital, according to the Japanese gastric cancer
treatment guideline, ESD is generally performed
based on two independent sets of clinical indications:
absolute indications for standard treatment, and
[3]
expanded indications for investigational treatment .
Furthermore, ESD is also performed for a small
number of patients with locally recurrent EGC or
EGC lesions outside the clinical indications for ESD,
particularly gastric tube cases, because the mortality
rate for surgical resection is remarkably high
[21-24]
. The
definitions for the characteristics of EGC lesions, such
as status of the stomach (normal stomach/remnant
stomach after a gastrectomy/gastric tube after an
esophagectomy), lesion location (upper/middle/lower
third of the stomach), gastric circumference (greater
curvature/lesser curvature/anterior wall/posterior wall),
tumor size, depth of invasion [mucosa (M)/submucosa
(SM)], presence of ulcerations, and histological type
(differentiated-type/undifferentiated-type), were based
on the Japanese classification of gastric carcinoma and
[3,25]
the Japanese gastric cancer treatment guidelines .
The term “gastric tube” refers to a stomach conduit
that has been pulled up into the thorax for use as an
[23,24]
esophageal substitute after an esophagectomy .
The histological type was defined according to the
major histological features of the lesion. Differentiated-
type adenocarcinoma included tubular adenocarcinoma
and papillary adenocarcinoma, while undifferentiated-
type adenocarcinoma included poorly differentiated
adenocarcinoma, signet-ring cell adenocarcinoma and
mucinous adenocarcinoma.
ESD procedure
The ESD procedure began with the identification of the
lesion and the marking of dots at a distance of about
5 mm outside of the lesion. After submucosal injection
using a saline solution or sodium hyaluronate (MucoUp;
Johnson & Johnson Corp., Tokyo, Japan) with epi­
nephrine, a 1- to 2-mm precut was made with an
electrosurgical needle knife (KD-1L-1; Olympus Optical,
Tokyo, Japan) or the Dual knife (KD-650Q; Olympus
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 Suzuki H et al . Delayed perforation from gastric ESD

Jaw hot biopsy forceps (Boston Scientific Japan, Tokyo,

Table 1 Clinicopathological findings of 4943 early gastric
cancer patients undergoing endoscopic submucosal dissection Japan)], or by grasping them with endoclips. The set-
up for the high-frequency generators for ESD along
Clinicopathological finding n (%) with the IT knife for early gastric cancer (ICC200 Erbe
Age (yr) Elektromedizin, Tübingen, Germany, ESG100 Olympus
median (range) 69 (27-96) Medical and VIO300D Erbe Elektromedizin, Tübingen,
< 70 2608 (52.8) Germany) is shown in Table 2. The risks and benefits
≥ 70 2335 (47.2)
of ESD were thoroughly explained to each patient,
Sex
Male 3930 (80.0)
and written informed consent was obtained from them
Female 1013 (20.0) in accordance with our institutional protocols prior to
Chronological periods treatment.
1st period: 1999-2005 2285 (46.2) The procedure time was defined as the time from
2nd period: 2006-2012 2658 (53.8)
circumferential marking around the lesion to the
Clinical indications
Absolute indications 2884 (58.3) completion of the ESD procedure. An en bloc resection
Expanded indications 1737 (35.1) was defined as a one-piece resection, and a piecemeal
Locally recurrent EGC 141 (2.9) resection was defined as the removal of a lesion in
Outside indications 181 (3.7) more than one piece
[3,25]
.
Stomach status
Normal stomach 4704 (95.2)
Remnant stomach 152 (3.1) Assessments of actual clinical management and
Gastric tube 87 (1.7) associated factors of delayed perforation
Location
We retrospectively assessed the incidence of delayed
Upper 904 (18.3)
Middle 2100 (42.5)
perforation and the actual clinical management of
Lower 1939 (39.2) this complication, including the need for emergency
Circumference surgery, the methods of conservative management,
Greater curvature 807 (16.3) and the median hospital stay. For the cases with
Lesser curvature 2005 (40.6)
delayed perforation requiring emergency surgery, the
Anterior wall 963 (19.5)
Posterior wall 1168 (23.6) reason for the emergency surgery was also clarified.
Size (mm) Finally, to determine the factors associated with delayed
median (range) 15 (0.4-120) perforation induced by gastric ESD, after excluding 123
≤ 20 3457 (69.9)
(2.5%) EGC patients with perforations that occurred
> 20 1486 (30.1)
Depth of invasion
during the ESD procedure, we retrospectively analyzed
M 4075 (82.4) the following clinicopathological factors among the
SM 868 (17.6) remaining 4820 EGC patients by comparing the ESD
Ulceration cases with delayed perforation with the ESD cases
Absent 4073 (82.4)
without perforation: age (< 70 years vs ≥ 70 years),
Present 870 (17.6)
Histological type sex (male vs female), chronological periods (1st
Differentiated 4581 (92.7) period: 1999-2005 vs 2nd period: 2006-2012), clinical
Undifferentiated 362 (7.3) indications for ESD (absolute indications vs expanded
Type of resection indications vs locally recurrent EGC vs outside
En bloc resection 4859 (98.3)
Piecemeal resection 84 (1.7)
indications), status of the stomach (normal stomach
Procedure time (h) vs remnant stomach after gastrectomy vs gastric tube
mean ± SD 1.4 ± 1.1 after esophagectomy), lesion location (upper/middle
<2 3811 (77.1) vs lower), gastric circumference (greater curvature
≥2 1132 (22.9)
vs lesser curvature vs anterior wall vs posterior wall),
tumor size (≤ 20 mm vs > 20 mm), depth of invasion
EGC: Early gastric cancer; M: Mucosa; SM: Submucosa.
(M vs SM), presence/absence of ulceration, histological
type (differentiated-type vs undifferentiated-type),
Optical, Tokyo, Japan), followed by a circumferential type of resection (en bloc resection vs piecemeal
mucosal incision outside the marking dots with an resection), and procedure time (< 2 h vs ≥ 2 h).
insulation-tipped (IT) diathermy knife (KD-610L;
Olympus Optical, Tokyo, Japan) or IT knife 2 (KD-611L; Definition of delayed perforation induced by gastric ESD
Olympus Optical, Tokyo, Japan). The submucosal Delayed perforation was identified by the sudden
layer was then dissected using an IT knife or an IT appearance of symptoms of peritoneal or mediastinal
knife 2 after an additional submucosal injection. Cases pleura irritation (gastric tube case) after the
with bleeding during or after the ESD procedure were completion of gastric ESD, with free air visible on
controlled by coagulating the bleeding vessels with the X-ray or computed tomography (CT) images and/or
IT knife itself and/or hemostatic forceps [Coagrasper with a gross defect observed endoscopically, although
(FD-410LR; Olympus Optical, Tokyo, Japan) and Radial endoscopically visible perforations did not occur

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 Suzuki H et al . Delayed perforation from gastric ESD

perforation. We performed a multivariate analysis

Table 2 Set-up for the high-frequency generators for
endoscopic submucosal dissection along with the IT knife for for clinicopathological factors that were significant in
early gastric cancer univariate analyses. A logistic regression analysis was
used for the multivariate analysis. All the statistical
Procedure Device Mode Output analyses were performed using the statistical analysis
ICC200 software SPSS, version 20 (SPSS Japan Inc., Tokyo,
Marking Needle knife Forced coag 20W Japan). A P-value < 0.05 was considered statistically
Precutting Needle knife ENDO CUT Effect 3, 80W
Mucosal IT knife ENDO CUT Effect 3, 80W
significant.
incision Needle knife
Submucosal IT knife ENDO CUT Effect 3, 80W
dissection Forced coag 50W RESULTS
Needle knife ENDO CUT Effect 3, 80W
Forced coag 50W
Incidence and actual management of delayed perforation
Endoscopic IT knife Forced coag 50W Delayed perforation occurred in 7 (0.1%) ESD cases
hemostasis Needle knife (Table 3). The median time until the occurrence of
Hot biopsy Soft coag 80W delayed perforation was 11 h (range, 6-172 h). As
Coagrasper
for the management of the delayed perforations, 3
ESG100
Marking Needle knife Forced coag 1 20W (43%) of the 7 delayed perforation cases underwent
Precutting Needle knife Pulse cut slow 40W emergency surgery, while 4 were conservatively
Mucosal IT knife Pulse cut slow 40W managed with nasogastric tube placement, fasting,
incision Needle knife and the use of intravenous antibiotics and proton
Submucosal IT knife Pulse cut slow 40W
dissection Forced coag 2 50W
pump inhibitors. Two of the 3 patients who required
Needle knife Pulse cut slow 40W emergency surgery received an omentoplasty or
Forced coag 2 50W simple closure of the perforation hole; however, one
Endoscopic IT knife Forced coag 2 50W patient underwent a distal gastrectomy because the
hemostasis Needle knife
ESD was evaluated as a non-curative resection. The
Hot biopsy Soft coag 80W
Coagrasper reason for the emergency surgery in these three
VIO300D cases was panperitonitis with remarkable clinical
Marking Needle knife Swift coag Effect 2, 50W symptoms, such as diffuse and severe tenderness
Precutting Needle knife ENDO CUT I Effect 2,
and/or defense musculaire. Among the 4 cases treated
CUT duration 2,
CUT interval 3 with conservative management, 2 were successfully
Mucosal IT knife ENDO CUT I or Q Effect 2, managed endoscopically using an endoloop-endoclip
[23,26]
incision CUT duration 2, technique . In this technique, the endoloop
CUT interval 3 snare was anchored with some clips to the normal
DRY CUT Effect 4, 50W [26]
Needle knife ENDO CUT I Effect 2,
mucosa around the delayed perforation defect . The
CUT duration 2, endoloop snare was tightened slightly, approximating
CUT interval 3 the borders of the defect. Finally, additional clips
DRY CUT Effect 4, 50W were placed to achieve complete closure. The median
Submucosal IT knife ENDO CUT I or Q Effect 2,
hospital stay in the delayed perforation cases was 18
dissection CUT duration 2,
CUT interval 3 d (range, 15-45 d). No delayed perforation-related
DRY CUT Effect 4, 50W deaths occurred in this series.
Swift coag Effect 5, 50W
Needle knife ENDO CUT I Effect 2,
CUT duration 2,
Factors associated with delayed perforation
CUT interval 3 Based on univariate analyses, outside clinical indi­
DRY CUT Effect 4, 50W cations, gastric tube cases, location in the upper/
Swift coag Effect 5, 50W middle third of the stomach, and procedure time ≥ 2 h
Endoscopic IT knife Swift coag Effect 5, 50W
were significantly associated with a delayed perforation
hemostasis Needle knife
Hot biopsy Soft coag Effect 5, 80W
(Table 4). No significant difference between the
Coagrasper rates of delayed perforation was observed when the
absolute indications (0.1%) and expanded indications
during the ESD procedure and no remarkable clinical (0.1%) were applied. Using a multivariate analysis for
symptoms were observed, suggesting perforation, just these cases, gastric tube cases (OR = 11.0; 95%CI:
after the ESD procedures. 1.7-73.3; P = 0.013) were found to be significantly
associated with delayed perforation (Table 4).
Statistical analysis A representative case (Case 4 in Table 3) with
The Fisher exact test or the χ test was used for the
2
delayed perforation is shown in Figures 1-5. A 64-year-
univariate analyses to assess the above-mentioned old woman underwent surveillance endoscopy after an
clinicopathological factors by comparing the ESD cases esophagectomy for esophageal cancer. The endoscopy
with delayed perforation with the ESD cases without showed a superficial depressed EGC lesion, 33 mm

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 Suzuki H et al . Delayed perforation from gastric ESD

Table 3 Clinical management of delayed perforation induced by gastric endoscopic submucosal dissection

Case Age (yr) Sex Stomach status Time until the occurrence Panperitonitis or severe Management of delayed Hospital stay
of delayed perforation (h) mediastinitis perforation (d)
1 68 Male Gastric tube 11 Absent Conservative management 45
2 75 Male Normal stomach 35 Absent Conservative management 18
3 80 Male Normal stomach 6 Absent Conservative management with 18
endoloop-endoclip technique
4 64 Female Gastric tube 7 Absent Conservative management with 25
endoloop-endoclip technique
5 73 Male Normal stomach 9 Present (Panperitonitis) Emergency surgery 15
6 62 Female Normal stomach 27 Present (Panperitonitis) Emergency surgery 18
7 56 Female Normal stomach 172 Present (Panperitonitis) Emergency surgery 15

Table 4 Factors associated with delayed perforation induced by gastric endoscopic submucosal dissection n (%)

Clinicopathological finding Univariate analysis Multivariate analysis,

OR (95%CI),
ESD cases without perforation ESD cases with delayed P value P value
(n = 4813) perforation (n = 7)
Age (yr) 1.00 -
< 70 2538 (99.8) 4 (0.2)
≥ 70 2275 (99.9) 3 (0.1)
Sex 0.16 -
Male 3828 (99.9) 4 (0.1)
Female 985 (99.7) 3 (0.3)
Chronological periods 1.00 -
1st period: 1999-2005 2194 (99.9) 3 (0.1)
2nd period: 2006-2012 2619 (99.8) 4 (0.2)
Clinical indications 0.02 NS
Outside indications 169 (98.8) 2 (1.2)
Other indications1 4644 (99.9) 5 (0.1)
Stomach status 0.006 11.0 (1.7-73.3), 0.013
Normal stomach/Remnant stomach 4732 (99.9) 5 (0.1)
Gastric tube 81 (97.6) 2 (2.4)
Location 0.047 NS
Upper/Middle 2894 (99.8) 7 (0.2)
Lower 1919 (100) 0 (0.0)
Circumference 0.09 -
Greater curvature 774 (99.6) 3 (0.4)
Others2 4039 (99.9) 4 (0.1)
Size (mm) 0.43 -
≤ 20 3395 (99.9) 4 (0.1)
> 20 1418 (99.8) 3 (0.2)
Depth of invasion 0.34 -
M 3988 (99.9) 5 (0.1)
SM 825 (99.8) 2 (0.2)
Ulceration 0.34 -
Absent 3982 (99.9) 5 (0.1)
Present 831 (99.8) 2 (0.2)
Histological type 0.09 -
Differentiated 4466 (99.9) 5 (0.1)
Undifferentiated 347 (99.4) 2 (0.6)
Type of resection 1.00 -
En bloc resection 4743 (99.9) 7 (0.1)
Piecemeal resection 70 (100) 0 (0.0)
Procedure time (h) 0.046 NS
<2 3758 (99.9) 3 (0.1)
≥2 1055 (99.6) 4 (0.4)

1
Other indications, absolute indications, expanded indications and locally recurrent early gastric cancer; 2Others, lesser curvature, anterior wall and
posterior wall. ESD: Endoscopic submucosal dissection; M: Mucosa; SM: Submucosa; NS: Not significant.

in size, at the greater curvature of the upper gastric ESD was performed for this lesion as a diagnostic
body of the gastric tube (Figure 1). The estimated procedure, and an en bloc resection with negative
tumor depth was the submucosa, and a biopsy margins was achieved without any complications.
revealed a poorly differentiated adenocarcinoma. As for the mucosal defect just after the completion

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 Suzuki H et al . Delayed perforation from gastric ESD
Figure 1 A superficial depressed early gastric cancer lesion located at the
greater curvature of the upper gastric body of the gastric tube.
Figure 2 Mucosal defect just after the completion of endoscopic
submucosal dissection (60 mm in size and half circumference).
Figure 3 A delayed perforation occurred 7 h after endoscopic submucosal
dissection.
of ESD, the size of the defect was 60 mm, and the
circumferential extent of the defect was one half of
the lumen of the gastric tube. At the proximal edge
of the ulceration, severe damage to the surface of the
muscularis propria as a result of electrical cautery was
seen, but no remarkable clinical symptoms, suggesting
perforation, were observed (Figure 2). Seven hours
after the ESD, a delayed perforation occurred with
chest pain (Figure 3). However, this patient did not
develop severe mediastinitis, so endoscopic closure
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Figure 4 The delayed perforation was successfully closed using the
endoloop-endoclip technique.
Figure 5 The delayed perforation had almost completely healed 15 d after
endoscopic submucosal dissection.
using the endoloop-endoclip technique was attempted
and successfully performed (Figure 4). In detail, the
endoloop snare was anchored with some clips to
the normal mucosa around the delayed perforation
[23,26]
defect . The endoloop snare was tightened slightly,
which approximated the borders of the defect. To
achieve complete closure, two endoloop snares with
additional clips were needed. The delayed perforation
had almost completely healed 15 d after ESD (Figure
5) and finally, the patient was conservatively managed
and was discharged 25 d after ESD.
DISCUSSION
Delayed perforation is reported to be a rare (incidence
of 0.43% to 0.45%) but serious complication induced
by gastric ESD that can sometimes require emergent
[6,14-20]
surgery . Although several reports have described
delayed perforation after gastric ESD, no published
report has thoroughly evaluated the various factors
that are associated with delayed perforation based on
data from a large series of consecutive EGC patients
[6,14-20]
undergoing ESD . Therefore, the present study is
significant because it clarified both the actual clinical
management and the associated factors of delayed
perforation induced by ESD for EGC based on data
12640 November 28, 2015|Volume 21|Issue 44|

from a large series of consecutive patients undergoing
gastric ESD.
In the present study, delayed perforation after
gastric ESD occurred in 7 (0.1%) ESD cases, and 3
(43%) of these 7 cases required emergency surgery.
[14]
Another report from Hanaoka et al
6 (0.45%) cases with delayed perforation among
1329 EGC lesions, and 5 (83%) of these 6 cases
underwent emergency surgery. In addition, Kato et
[16]
al reported 2 (0.43%) cases of delayed perforation
occurring after the completion of ESD among 468
cases of gastric non-invasive neoplasia, both of which
required emergency surgery. Several case reports
of delayed perforation after gastric ESD that were
successfully managed conservatively have also been
[15,17,18,20]
reported . Thus, although a small number of
cases of delayed perforation might be successfully
managed conservatively (9 among 21 delayed
perforation patients, including 14 patients in previous
[14-20]
reports and our 7 patients, were successfully
managed conservatively), we need to remember that
in delayed perforation cases, emergency surgery may
be required with a high probability and conservative
management might not always be feasible. In the near
future, the establishment of effective conservative
treatments may reduce the rate of delayed perforation
[20]
cases requiring emergency surgery . The early
recognition of the onset of delayed perforation after
the sudden appearance of symptoms of peritoneal
or mediastinal pleura irritation (gastric tube cases)
within 24 h after gastric ESD followed by prompt
conservative treatment may be useful for avoiding
emergency surgery. In the case of delayed perforation
without any findings of panperitonitis or severe
mediastinitis (gastric tube cases), the endoloop-
endoclip technique under CO2 insufflation might make
it possible to close defects of the gastric wall caused
by delayed perforation in a conservative manner, as
[23,26,27]
in our representative case . CO2 insufflation has
increasingly been used instead of air insufflation to
minimize pneumoperitoneum caused by perforation .
The results of the present study also showed that
gastric tube cases were an independent risk factor
associated with delayed perforation after ESD, based
on a large consecutive series of EGC patients. Hanaoka
[14]
et al reported that 5 out of 6 delayed perforations
occurred in the upper third of the stomach; however,
this report represented a case series of delayed
perforations without any assessment of the risk factors
associated with delayed perforation by comparing
the ESD cases with delayed perforation with ESD
cases without perforation. The reason for the high
frequency of delayed perforations in the gastric tube
was uncertain, but reduced vascular circulation of the
reconstructed gastric tube may have resulted in slower
[23]
ESD ulcer healing . In addition, Hanaoka et al
reported that the mechanism of delayed perforation
was thought to be due to electrical cautery during
the submucosal dissection or repeated coagulation
WJG|www.wjgnet.com
Suzuki H et al . Delayed perforation from gastric ESD
causing ischemic changes to the gastric wall, resulting
[28]
in necrosis. Furthermore, Onogi et al reported the
existence of a “transmural air leak” after gastric ESD,
as detected by a CT examination. In the present study,
we cannot rule out the possible existence of severe
described damage to the surface of the muscularis propria with
a transmural air leak, since we did not perform a CT
examination in most of the cases undergoing gastric
ESD. Thus, there might be a possibility of developing
delayed perforation from severe damage to the
surface of the muscularis propria with transmural air
leaks after the ESD procedure. More recently, the
feasibility and effectiveness of ESD for gastric tube
cancer after esophagectomy have been reported
[23,24]
.
Thus, awareness of this finding is important before
the widespread use of this treatment, and in cases
of ESD for gastric tube cancer, it might be better to
avoid excessive electrical cautery during submucosal
dissection or repeated coagulation so as to prevent
delayed perforation.
Our study had several limitations. First, the results
of the present study were based on retrospective
assessments of the medical records of patients with
gastric ESD, although these data were based on a
large consecutive series of gastric ESDs. Second,
the present study was conducted at a single major
referral cancer center in a large metropolitan area of
Japan with many highly experienced endoscopists
with specific expertise in ESD. Thus, a prospective
multicenter study is required for a more precise
evaluation of the actual clinical management and the
associated factors of delayed perforation induced by
gastric ESD. Several multicenter prospective cohort
[29-31]
studies on gastric ESD are currently underway .
In conclusion, endoscopists must be aware of not
only the identified factors associated with delayed
perforation induced by gastric ESD, but also how to
treat this complication effectively and promptly.
ACKNOWLEDGMENTS
[27]
We thank Dr. Hiroyuki Ono and Dr. Takuji Gotoda (our
mentors of National Cancer Center Hospital in Tokyo)
for their efforts in developing ESD.
COMMENTS
COMMENTS
Background
Delayed perforation after gastric endoscopic submucosal dissection (ESD)
is a rare but serious complication that sometimes requires emergent surgery.
Therefore, the actual clinical management and the associated factors of
delayed perforation after gastric ESD should be clarified to minimize its
incidence and to treat this complication effectively and promptly.
Research frontiers
[14] Although several reports have described delayed perforation after gastric ESD,
no published report has thoroughly evaluated the various factors associated
with delayed perforation in addition to the actual clinical management of
this complication based on data from a large series of consecutive patients
undergoing gastric ESD.
12641 November 28, 2015|Volume 21|Issue 44|
 Suzuki H et al . Delayed perforation from gastric ESD
Innovations and breakthroughs
The early recognition of the onset of delayed perforation after the sudden
appearance of symptoms of peritoneal or mediastinal pleura irritation (gastric
tube cases) within 24 h after gastric ESD followed by prompt conservative
treatment may be useful for avoiding emergency surgery. In addition, in cases
of ESD for gastric tube cancer, it might be better to avoid excessive electrical
cautery during submucosal dissection or repeated coagulation so as to prevent
delayed perforation.
Applications
The results of the present study suggest that endoscopists should be aware of
not only the identified factors associated with delayed perforation, but also how
to treat this complication effectively and promptly.
Terminology
Bleeding and perforation are major complications of gastric ESD. ESD-related
perforations can be subdivided into perforations that occur during gastric ESD
and delayed perforations occurring after the completion of gastric ESD. Most
perforations occur during gastric ESD, and the majority of perforation cases can
be treated conservatively using complete endoscopic closure with endoclips. In
contrast, delayed perforation is a rare but serious complication that sometimes
requires emergent surgery.
Peer-review
This study is significant because it clarified both the actual clinical management
and the associated factors of delayed perforation based on data from a large
consecutive series of patients undergoing gastric ESD.
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P- Reviewer: Chung JW, Gonzalez N, Kim GH, Man-I M, Matsumoto
S- Editor: Yu J L- Editor: Wang TQ E- Editor: Ma S
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